Gestational diabetes and maternal obesity are associated with sex-specific changes in miRNA and target gene expression in the fetus

Joshi, Apoorva; Azuma, Rikka; Akumuo, Rita; Goetzl, Laura; Pinney, Sara E.

doi:10.1038/s41366-019-0485-y

Cited by 26 publications

(19 citation statements)

References 60 publications

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“…For example, small non-coding mRNAS, or miRNAs are epigenetic regulatory elements which perform fundamental roles in normal development, and can act as post transcriptional modifiers to control gene expression and translation [30]. Evidence suggests that sex differences exist in miRNA expression in the fetal brain of rodents [31], as well as in humans [32,33], and that maternal nutrition can alter miRNA expression in a sex-specific manner [34]. Furthermore, although in the context of osteoblast differentiation, previous studies have identified multiple miRNAs shown to be capable of regulating SATB2 [35,36], thus it is feasible that differential post-transcriptional regulatory activity contributes to SATB2 sex differences in the offspring VMN.…”

Section: Discussionmentioning

confidence: 99%

Maternal Obesity Modulates Expression of Satb2 in Hypothalamic VMN of Female Offspring

Glendining

Fisher

Jasoni

2020

Life

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Maternal obesity during pregnancy is associated with a greater risk of poor health outcomes in offspring, including obesity, metabolic disorders, and anxiety, however the incidence of these diseases differs for males and females. Similarly, animal models of maternal obesity have reported sex differences in offspring, for both metabolic outcomes and anxiety-like behaviors. The ventromedial nucleus of the hypothalamus (VMN) is a brain region known to be involved in the regulation of both metabolism and anxiety, and is well documented to be sexually dimorphic. As the VMN is largely composed of glutamatergic neurons, which are important for its functions in modulating metabolism and anxiety, we hypothesized that maternal obesity may alter the number of glutamatergic neurons in the offspring VMN. We used a mouse model of a maternal high-fat diet (mHFD), to examine mRNA expression of the glutamatergic neuronal marker Satb2 in the mediobasal hypothalamus of control and mHFD offspring at GD17.5. We found sex differences in Satb2 expression, with mHFD-induced upregulation of Satb2 mRNA in the mediobasal hypothalamus of female offspring, compared to controls, but not males. Using immunohistochemistry, we found an increase in the number of SATB2-positive cells in female mHFD offspring VMN, compared to controls, which was localized to the rostral region of the nucleus. These data provide evidence that maternal nutrition during gestation alters the developing VMN, possibly increasing its glutamatergic drive of offspring in a sex-specific manner, which may contribute to sexual dimorphism in offspring health outcomes later in life.

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Section: Discussionmentioning

confidence: 99%

Maternal Obesity Modulates Expression of Satb2 in Hypothalamic VMN of Female Offspring

Glendining

Fisher

Jasoni

2020

Life

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“…Nevertheless, Brass et al [ 38 ] showed that placental uptake of oleic acid was suppressed and that the expression of the placental transporter CD36 was lower in male but not in female newborn of obese women. Recently, it was shown that miRNA expression in amniotic fluid and fetal hepatocytes is dependent on sex in offspring of women with GDM or obesity, although the mechanisms contributing to this phenomenon remain unknown [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Relative Contribution of Gestational Weight Gain, Gestational Diabetes, and Maternal Obesity to Neonatal Fat Mass

et al. 2020

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Maternal nutritional and metabolic status influence fetal growth. This study investigated the contribution of gestational weight gain (GWG), gestational diabetes (GDM), and maternal obesity to birthweight and newborn body fat. It is a secondary analysis of a prospective study including 204 women with a pregestational body mass index (BMI) of 18.5–24.9 kg/m2 and 219 women with BMI ≥ 30 kg/m2. GDM was screened in the second and third trimester and was treated by dietary intervention, and insulin if required. Maternal obesity had the greatest effect on skinfolds (+1.4 mm) and cord leptin (+3.5 ng/mL), but no effect on birthweight. GWG was associated with increased birthweight and skinfolds thickness, independently from GDM and maternal obesity. There was an interaction between third trimester weight gain and GDM on birthweight and cord leptin, but not with maternal obesity. On average, +1 kg in third trimester was associated with +13 g in birthweight and with +0.64 ng/mL in cord leptin, and a further 32 g and 0.89 ng/mL increase in diabetic mothers, respectively. Maternal obesity is the main contributor to neonatal body fat. There is an independent association between third trimester weight gain, birthweight, and neonatal body fat, enhanced by GDM despite intensive treatment.

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“…According to Joshi et al, GDM confers an effect on offspring mediated by gender-specific alterations in miRNA and target-gene expression in the fetus [ 159 ]. miRNA was analyzed in the amniotic fluid (AF) of 20 women with and 20 without GDM in the second trimester [ 159 ]. The AF of women with GDM was found to be upregulated by miR-199a-3p , miR-1268a , and miR-503-5p .…”

Section: Epigenetic Modifications In Gdmmentioning

confidence: 99%

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

Samra

Jelinek

Alsafar

et al. 2022

IJMS

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One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.

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Gestational diabetes and maternal obesity are associated with sex-specific changes in miRNA and target gene expression in the fetus

Cited by 26 publications

References 60 publications

Maternal Obesity Modulates Expression of Satb2 in Hypothalamic VMN of Female Offspring

Maternal Obesity Modulates Expression of Satb2 in Hypothalamic VMN of Female Offspring

Relative Contribution of Gestational Weight Gain, Gestational Diabetes, and Maternal Obesity to Neonatal Fat Mass

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

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